Consider patient risk factors when interpreting tests for acute HIV infection

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Three case reports from the United States highlight shortcomings in a method of HIV testing that is being employed to detect early infection with HIV. In the February 1st edition of Clinical Infectious Diseases, investigators from Washington State report on instances when HIV nucleic acid testing (NAT) and HIV antibody tests failed to detect HIV infection in individuals with recent exposure to HIV and symptoms consistent with HIV seroconversion illness. The cases underlined the importance of interpreting test results in the context of individual HIV risk assessments.

Because HIV antibody tests may be unable to detect HIV infection for up to three months after infection with HIV, pooled HIV NAT is increasingly being used to detect acute HIV infection. However, like HIV antibody tests, pooled NAT testing does not have 100% sensitivity or specificity and the results need careful interpretation, taking into account the local epidemiology of HIV.

Investigators from Washington State in the US encountered three unusual cases involving individuals being screened for acute HIV infection.


enzyme-linked immunosorbent assay (ELISA)

A diagnostic test in which a signal produced by an enzymatic reaction is used to detect and quantify the amount of a specific substance in a solution. Can be used to detect antibodies to HIV, p24 antigen or other substances.

acute infection

The very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).


A rash is an area of irritated or swollen skin, affecting its colour, appearance, or texture. It may be localised in one part of the body or affect all the skin. Rashes are usually caused by inflammation of the skin, which can have many causes, including an allergic reaction to a medicine.


Tiredness, often severe (exhaustion).


ribonucleic acid (RNA)

The chemical structure that carries genetic instructions for protein synthesis. Although DNA is the primary genetic material of cells, RNA is the genetic material for some viruses like HIV.


The first two patients were a gay couple, patient A and B, who had engaged in unprotected anal sex with each other and outside of their relationship. Patient A reported symptoms of fever, rash, headaches, night sweats, swollen lymph nodes in the neck, fatigue, and muscle pain for four days. Upon physical examination he had a rash on his face, torso and both arms. His HIV diagnosis was confirmed by an HIV RNA test which indicated the patient had a viral load of 70,000 copies/ml.

Patient B was asymptomatic on his first visit. He tested HIV-negative on a standard ELISA antibody test and pooled HIV RNA test. A week later, he started experiencing symptoms of fever, headache, fatigue and muscle pain. Two days later, he was re-tested, had a viral load of 621,000 copies/ml and a CD4 cell count of 219 cells/mm3. A week after that, he tested negative on an antibody test and had a very high viral load - 2,515,000 copies/ml. His physician initiated antiretroviral therapy.

The clinical history and viral sequence analysis confirmed patient A transmitted HIV to patient B.

A frozen unpooled HIV NAT serum specimen of patient B, taken four days after his exposure, showed no evidence of HIV infection.

Patient C, presented nine days after unprotected receptive anal sex with a partner of unknown HIV status. His symptoms were sore throat, diarrhoea and nasal congestion. He tested negative on ELISA and Western blot assays, but had a viral load of 923 copies/ml, and a CD4 cell count of 1,264 cells/mm3. A week later, he again tested negative on the ELISA assay, but had a high viral load of a little over 1,000,000 copies/ml. The following week, he, once again, tested negative on ELISA and Western blot assays but had an enormous viral load - 26,785,000 copies/ml. His CD4 cell count had fallen dramatically to 336 cells/mm3.

The investigators believe that these three cases highlight the failure of routine antibody testing and HIV NAT to correctly identify individuals during acute HIV infection. They stress that pooled HIV NAT tests may provide a false-negative result for individuals at high risk of HIV infection. Healthcare providers should, the researchers write, be aware of the various characteristics of HIV tests, such as ELISA, HIV NAT and rapid HIV antibody test. Additionally, the cases underline the importance of recognising the symptoms of acute HIV infection and the offering of appropriate care and treatment to individuals.


Stekler J et al. Screening for acute HIV infection: lessons learned. Clin Infect Dis 44: 459-461, 2007